Oral composition
An oral composition comprising cetylpyridinium chloride and a N.sup..alpha. -longer acyl basic amino acid lower alkyl ester or a salt thereof. The oral composition of the present invention promotes adsorption of cetylpyridinium chloride as a bactericide to the surfaces of teeth and shows excellent prevention of formation of dental plaque and dental caries.
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The present invention relates to a composition for the oral cavity. More particularly, it relates to an oral composition wherein adsorption of cetylpyridinium chloride as a bactericide to the surfaces of teeth is promoted.
BACKGROUND OF THE INVENTIONDental plaque is formed by adsorption and propagation of intraoral bacteria such as Streptococcus mutans and the like on the surfaces of teeth. It is well known that dental plaque is the cause of dental caries and is also the cause of gingivitis or alveolar pyorrhea. Therefore, it is important to remove dental plaque and to prevent adhesion of it (plaque control) for oral sanitation.
Among the plaque control methods, the method which is performed most commonly is that for removing dental plaque mechanically by brushing, that is, by using a toothbrush. However, in order to remove dental plaque completely by brushing, high-level brushing technique is needed. In practice, almost all people are conducting insufficient brushing and, therefore, the rate of diseases such as dental caries, gingivitis and alveolar pyorrhea is not reduced despite brushing.
Accordingly, in order to compensate brushing, or to substitute for brushing, a chemical plaque control method has been studied. The pyridinium compounds having C.sub.8-18 straight or blanched chain alkyl group are known. Among them, the compound of which efficacy and safety are clinically acknowledged is cetylpyridinium chloride.
It is known that cetylpyridinium chloride is a compound represented by the formula: ##STR1## and it has a bactericidal action and is easily to adsorbed to oral mucosa or the surfaces of teeth. Thereby, it is considered that adsorption of intraoral bacteria to the surfaces of teeth is prevented and, further, formation of dental plaque is prevented. However, a study on promoting adsorption of such cetylpyridinium chloride to the surfaces of teeth or on improving it's effect has not been performed yet.
The present inventors have intensively studied to promote retention of cetylpyridinium chloride in the oral cavity, particularly adsorption of it to the surfaces of teeth and to enhance the effect of preventing formation of bacterial plaque. As a result, it has been found that, when cetylpyridinium chloride is used in combination with an N.sup..alpha. -longer acyl basic amino acid lower alkyl ester or a salt thereof, adsorption of cetylpyridinium chloride to the surfaces of teeth is greatly enhanced. Thus, the present invention has been completed.
DISCLOSURE OF THE INVENTIONAccording to the present invention, there is provided an oral composition comprising cetylpyridinium chloride and an N.sup..alpha. -longer acyl basic amino acid lower alkyl ester or a salt thereof. According to the present invention, an oral composition which promotes adsorption of cetylpyridinium chloride to the surfaces of teeth and has excellent effect for preventing formation of dental plaque and dental caries can be obtained.
Cetylpyridinium chloride is normally formulated into the composition in an amount of more than 0.002 % by weight, preferably more than 0.01 % by weight. In view of bactericidal effect, the upper limit of the amount of cetylpyridinium chloride is not specifically limited. Considering the fact that cetylpyridinium chloride has a bitter taste and is likely to color teeth when the amount is too large, or influence on oral mucosa and the like, it is normally preferred that the amount is less than 1 % by weight.
As the basic amino acid part of the N.sup..alpha. -longer acyl basic amino acid lower alkyl ester to be used, ornithine, lysine and arginine are particularly preferred and it may be either an optical isomer or racemate thereof. The acyl group thereof is a saturated or unsaturated natural or synthetic fatty acid residue having 8 to 22 carbon atoms, for example, it may be a natural system mixed fatty acid residue such as coconut oil fatty acid, tallow fatty acid residue and the like, in addition to a monofatty acid residue such as lauroyl, myristyl, stearoyl group and the like. Further, it may also be a lower alkyl ester, such as methyl ester, ethyl ester and propyl ester are.
Examples of the salt of the N.sup..alpha. -longer basic amino acid lower alkyl ester include an inorganic acid salt such as hydrochloride, sulfate, etc. or an organic acid salt such as acetate, tartrate, citrate, p-toluenesulfonate, fatty acid salt, acidic amino acid salt, etc. Among them, glutamate, pyroglutamate, acetate and citrate are preferred.
In the present invention, the N.sup..alpha. -longer basic amino acid lower alkyl ester or a salt thereof is that which promotes adsorption of cetylpyridinium chloride to the surfaces of teeth. The weight ratio thereof is at least 1/5, normally 1/5 to 10 based on the weight of cetylpyridinium chloride. When the ratio is too small, the effect of promoting adsorption of cetylpyridinium chloride to teeth becomes insufficient.
The oral composition of the present invention can be prepared in the form of tooth powder, dentifrice, mouthwash, troches and the like by formulating desired ingredients according to a conventional method and, further, it can be sprayed in the oral cavity as an aerosol. Further, it can be used for a liniment and also used after being impregnated in a dental floss or toothpick.
The other ingredients formulated may be any ingredients which can be used in this kind of compositions in so far as they do not inhibit adsorption of cetylpyridinium chloride to the surfaces of teeth and its bactericidal action. In the case of using vesicants or solubilizers, anionic ingredients are not preferred. It has been found that, when using nonionic or cationic ingredients, particularly, polyoxyethylene polyoxypropylene glycol, ethylenediaminetetrapolyoxyethylene polyoxypropylene glycol and the like, the effect of cetylpyridinium chloride is further improved.
EXAMPLESThe following Experiments and Examples further illustrate the present invention in detail but are not to be construed to limit the scope thereof. In Experiments and Examples, all percentages are by weight unless otherwise stated.
Experiment 1Adsorption test of cetylpyridinium chloride to the
surfaces of teeth
The composition of enamel of the surfaces of teeth consists of inorganic mineral (97 %), organic material (1%) and water content (2 %), and a main ingredient of the mineral is calcium phosphate which is referred to as hydroxyapatite [Ca.sub.10 (PO.sub.4).sub.6 (OH).sub.2 ].
As a model of enamel of teeth, that obtained by dipping a hydroxyapatite disc [Bio-Gel HTP manufactured by Bio. Rad. Laboratories Co., U.S.A., 13 mm.phi. .times.250 mg; prepared by making tablets at 150 kg/cm.sup.2 and sintering at 600.degree. C. for 6 hours] in human saliva at 37.degree. C. for 18 hours was used. By dipping in saliva, saliva mucoprotein, etc. was adsorbed to the surface of hydroxyapatite to be allowed to simulate an actual state of tooth enamel wetted with saliva. This hydroxyapatite disc treated with saliva was placed in a test tube, followed by the addition of an aqueous 0.05 % cetylpyridinium chloride (manufactured by Merck Co.) solution (1 ml) and shaking at 37.degree. C. for 30 minutes. Thereafter, it was washed with water (6 ml) and extracted with an extraction solvent [50 mM sodium lauryl sulfate, 40 mM citrate buffer (pH 3.0)/acetonitrile =30/70] to form a sample for high speed liquid chromatography. In the case of high speed liquid chromatography, Lichrosorb RP select B (4.0 mm.phi. .times.250 mm) was used as a separation column and a extraction solvent was used as an eluent. The flow rate was 1 ml/minutes and detection of cetylpyridinium was conducted by measuring absorbance with 258 nm. Further, by using a calibration curve made by a standard solution of cetylpyridinium chloride, the amount of cetylpyridinium chloride was determined.
Likewise, after an apatite disc treated with saliva was dipped in a mixed solution in which various additives as shown in Table 1 were added to 0.05 % cetylpyridinium chloride in an amount of 0.1 %, respectively, the amount of cetylpyridinium chloride was determined. Further, regarding N.sup..alpha. -cocoyl-L-arginine ethyl ester pyrrolidone carboxylate among the additives which showed the effect for enhancing the amount of cetylpyridinium chloride adsorbed on the apatite disc, by varying in amount between 0.005, 0.01 and 0.05 %, respectively, the influence of the concentration on the amount of cetylpyridinium chloride adsorbed was confirmed. The results are also shown in Table 1.
TABLE 1
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Amount of cetylpyridinium
chloride (.mu.g/disc)
Compound Initial After 3 hours
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0.05% Cetylpyridinium chloride
170 63
0.05% Cetylpyridinium chloride +
411 321
0.01% N.sup..alpha. -cocoyl-L-arginine
methyl ester hydrochloride
0.05% Cetylpyridinium chloride +
436 336
0.1% N.sup..alpha. -lauroyl-L-arginine
methyl ester pyrrolidone
carboxylate
0.05% Cetylpyridinium chloride +
438 346
0.1% N.sup..alpha. -cocoyl-L-arginine ethyl
ester pyrrolidone carboxylate
0.05% Cetylpyridinium chloride +
424 330
0.1% N.sup..alpha. -palmitol-L-lysine
methyl ester acetate
0.05% Cetylpyridinium chloride +
59 18
0.1% sodium N.sup..alpha. -lauroyl methyl
taurine
0.05% Cetylpyridinium chloride +
173 60
0.1% sodium N.sup..alpha. -lauroyl-methyl-b-
alanine
0.05% Cetylpyridinium chloride +
175 119
0.005% N.sup..alpha. -cocoyl-L-arginine
ester pyrrolidone carboxylate
0.05% Cetylpyridinium chloride +
331 242
0.01% N.sup..alpha. -cocoyl-L-arginine
ethyl ester pyrrolidone
carboxylate
0.05% Cetylpyridinium chloride +
392 294
0.05% N.sup..alpha. -cocoyl-L-arginine
ethyl ester pyrrolidone
carboxylate
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As is shown in Table 1, when a N.sup..alpha. -longer acyl basic amino acid lower alkyl ester is formulated, cetylpyridinium chloride is specifically adsorbed to the hydroxyapatite disc and it is necessary that the weight ratio is more than 1/5 based on the weight of cetylpyridinium chloride.
EXPERIMENT 2Since cetylpyridinium chloride is sometimes inactivated in the case of forming a salt with an acidic substance, retention of bactericidal activity was also tested as follows.
Regarding a sample wherein adsorption of cetylpyridinium chloride to the hydroxyapatite disc was enhanced by adding the N.sup..alpha. -longer acyl basic amino acid lower alkyl ester, a disc was suspended to a 5 % sucrose BHI medium. Then, one loopful of the Streptococcus mutans ATCC 25175 strain was inoculated and cultivated at 37.degree. C. for 18 hours. As a result, adhesion of plaque to the hydroxyapatite disc was not observed and it was confirmed that cetylpyridinium chloride adsorbed on the hydroxyapatite disc retains bactericidal activity.
EXAMPLE 1According to the following formulation, a toothpaste was prepared by degassing, kneading and stirring according to a conventional method.
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Ingredients % by weight
______________________________________
Calcium hydrogenphosphate
20.0
Polyoxyethylene polyoxypropylene
30.0
glycol
Glycerin 10.0
Cetylpyridinium chloride
0.1
N.sup..alpha. -lauroyl-L-arginine methyl ester
0.05
pyrrolidone carboxylate
Saccharin sodium 0.2
Flavor 1.0
Distilled water up to 100%
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EXAMPLE 2
According to the following formulation, a toothpaste was prepared by degassing, kneading and stirring according to a conventional method.
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Ingredients % by weight
______________________________________
Calcium carbonate 35.0
Hydroxyethylcellulose
1.5
Ethylenediamine tetrapolyoxy-
5.0
ethylene polyoxypropylene glycol
Sorbitol 30.0
Cetylpyridinium chloride
0.01
N.sup..alpha. -cocoyl-L-arginine methyl
0.01
ester hydrochloride
Saccharin sodium 0.1
Flavor 1.0
Distilled water up to 100%
______________________________________
EXAMPLE 3
According to the following formulation, a liquid mouthwash was prepared by mixing with stirring according to a conventional method.
______________________________________
Ingredients % by weight
______________________________________
Ethanol 10.0
Glycerin 10.0
Polyoxyethylene polyoxypropylene
1.5
glycol
Saccharin sodium 0.02
Cetylpyridinium chloride
0.05
N.sup..alpha. -cocoyl-L-arginine ethyl
0.1
ester pyrrolidone carboxylate
Flavor 0.3
Distilled water up to 100%
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EXAMPLE 4
A yarn of 630 deniers comprising a plurality of fine denier filaments of 6,6-nylon being twisted was dipped in the mixed solution of the following formulation, passed through a drying tube at 50.degree. C. and spooled with vaporizing ethanol to produce a dental floss.
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Ingredients % by weight
______________________________________
Cetylpyridinium chloride
5.0
N.sup..alpha. cocoyl-L-arginine ethyl ester
10.0
pyrrolidone carboxylate
Ethanol 85.0
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Claims
1. An oral composition consisting essentially of a bactericidal effective amount of cetylpyridinium chloride and a N.sup..alpha. -longer acyl basic amino acid lower alkyl ester or a salt thereof in an amount effective to promote the adsorption of cetylpyridinium chloride to the surfaces of teeth, wherein the amount of cetylpyridinium chloride is from 0.002% to 1% by weight of the composition.
2. An oral composition according to claim 1, wherein the weight ratio of the N.sup..alpha. -longer acyl basic amino acid lower alkyl ester to cetylpyridinium chloride is from 1/5 to 10.
3. An oral composition according to claim 2, wherein the N.sup..alpha. -longer acyl basic amino acid lower alkyl ester is selected from the group consisting of N.sup..alpha. -cocoyl-L-arginine methyl ester hydrochloride, N.sup..alpha. -lauroyl-L-arginine methyl ester pyrrolidone carboxylate, N.sup..alpha. -cocoyl -L-arginine ethyl ester pyrrolidone carboxylate, and N.sup..alpha. -palmitoyl-L-lysine-methyl ester acetate.
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Type: Grant
Filed: Jan 28, 1992
Date of Patent: Nov 30, 1993
Assignee: Sunstar Kabushiki Kaisha (Osaka)
Inventors: Hidehiko Ohtsuki (Takatsuki), Tomomi Fujita (Suita)
Primary Examiner: Shep K. Rose
Law Firm: Wegner, Cantor, Mueller & Player
Application Number: 7/828,793
International Classification: A61K 716; A61K 722;
